TGFβ1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.
TGFβ1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.
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DOI：
10.1158/1078-0432.ccr-17-1904
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发表时间：
2018-05-01
期刊：
影响因子：
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通讯作者：
Li G
中科院分区：
文献类型：
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作者：
Tao Y;Sturgis EM;Huang Z;Wang Y;Wei P;Wang JR;Wei Q;Li G
转化生长因子-β1 (TGF-β1) 在炎症和免疫反应以及治疗反应和生存中发挥着关键作用。 TGF-β1 变异体可能会影响其表达水平或功能效率，从而改变 HPV 阳性口咽鳞状细胞癌 (SCCOP) 的肿瘤状态和存活率。我们测定了 564 名接受放疗或放化疗的 SCCOP 患者的肿瘤 HPV16 状态，并对三种 TGF-β1 多态性进行了基因分型。使用单变量和多变量 Cox 模型来评估三种多态性与生存之间的关联。总体而言，85% 的患者（564 名患者中的 482 名）患有 HPV16 阳性 SCCOP。我们发现 TGF-β1 rs1982073 与生存率具有统计学显着相关性，而 TGF-β1 rs1800469 和 TGF-β1 rs1800471 则没有。与相应常见纯合 TT 基因型患者相比，TGF-β1 rs1982073 CT/CC 变异基因型患者的总体生存率、疾病特异性生存率和无病生存率显着更高（所有对数秩：P <0.001）。此外，这些基因型与总体死亡、疾病死亡和多变量调整后复发风险降低约 5 倍显着相关。此外，按肿瘤HPV状态进行的分层分析表明，TGF-β1 rs1982073多态性仅在HPV16阳性SCCOP患者中发现对生存的显着影响。最后，进一步表征了这些变体的功能相关性。我们的研究结果支持TGF-β1 rs1982073多态性在SCCOP的预后中发挥重要作用，特别是在接受放化疗的HPV16阳性SCCOP患者中。需要更大样本量的前瞻性研究来证实这些发现。
Transforming growth factor-β1 (TGF-β1) plays a critical role in inflammation and immune responses and treatment response and survival. TGF-β1 variants may affect its expression level or functional efficiency, thus modifying tumor status and survival in HPV-positive squamous cell carcinoma of the oropharynx (SCCOP). We determined tumor HPV16 status and genotyped three TGF-β1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy or chemoradiation. Univariate and multivariable Cox models were used to evaluate the associations between the three polymorphisms and survival. Overall, 85% of patients (482 of 564) had HPV16-positive SCCOP. We found that TGF-β1 rs1982073 had statistically significant associations with survival, while TGF-β1 rs1800469 and TGF-β1 rs1800471 did not. Patients with TGF-β1 rs1982073 CT/CC variant genotypes had significantly better overall, disease-specific, and disease-free survival compared with those with the corresponding common homozygous TT genotype (all log-rank: P <0.001). Furthermore, these genotypes were significantly associated with an approximately 5 times reduced risk of overall death, death owing to disease, and recurrence after multivariable adjustment. Moreover, the stratified analyses by tumor HPV status indicated that the significant effects of TGF-β1 rs1982073 polymorphism on survival were found among HPV16-positive SCCOP patients only. Finally, the functional relevance of these variants was further characterized. Our findings support that the TGF-β1 rs1982073 polymorphism plays a significant role in the prognosis of SCCOP, especially in HPV16-positive SCCOP patients treated with chemoradiation. Prospective studies with larger sample sizes are needed to confirm these findings.